Autism is a serious behaviorally defined disorder whose prevalence appears to be increasing dramatically. In response to Program Announcement PA-01-051, we propose a nested case control study to evaluate the association between the risk of autism and several biologic markers with the potential to impact neurodevelopment that can be measured in archived maternal sera specimens collected in early pregnancy and neonatal blood specimens collected in the first few days of life. The study population will be drawn from the cohort of women who were pregnant in Orange county, California, who participated in the state-mandated prenatal expanded alpha-fetoprotein screening program (XAFP), and who delivered a live born infant between July 2000 - September 2001. Three groups of children born to women in the cohort will be identified. Cases (n=100) will be children enrolled in the Regional Center of Orange County (RCOC) with a diagnosis of autism with or without mental retardation (MR). One set of controls will be children with MR but not autism (n=100), also identified from RCOC. The second set of controls will be general population controls (n=100), randomly sampled from the population of live births in Orange and surrounding counties, frequency matched to the cases on birth year, county of residence at birth, and gender. Verification of autism and MR diagnoses will be based on thorough abstraction of diagnostic and clinical information contained in the RCOC medical records followed by expert clinical review. Maternal early pregnancy blood specimens will be obtained from the Project Baby's Breath maternal XAFP specimen bank. This unique resource will allow us to conduct a retrospective nested case-control study using prospectively collected biologic specimens from a time period critical to fetal neurodevelopment. Several analytes that are known or suspected to play a key role in early brain development will be examined, including antibodies to viral infections, cytokines, autoantibodies to neural tissue and thyroid peroxidase, free thyroxine, TSH, testosterone, estradiol, selected neuropeptides and neurotrophins, and selected metals. We will also incorporate results from routine neonatal screening, and demographic and perinatal data routinely recorded on the birth certificate. Results from this study will provide direction for future investigations of prenatal and neonatal specimens already archived in California and investigations of specimen banks now being created in Norway and other countries.